The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the cent...The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.展开更多
Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine ...Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.展开更多
The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have ena...The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.展开更多
BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical perf...BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.展开更多
Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a...Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a field and their ordered and supported effects (synergy) that must be realized for the “organized transformation” of the space and matter. Using path integrals, these transformations are decoded and their quantum principles are shown.展开更多
Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and there...Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography(EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.展开更多
BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocard...BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocardiography(ECG),myocardial per-fusion imaging(MPI),and stress echocardiography have been the first-line stra-tegies.However,coronary computed tomography angiography(CCTA),an anatomic imaging modality,is increasingly used for its ability to directly visualize coronary artery stenoses and plaque burden.Despite growing adoption,the comparative effectiveness of CCTA and stress testing in terms of diagnostic accuracy,prognostic value,and clinical outcomes in stable angina remains an area of active debate.AIM To compare the diagnostic and prognostic performance of CCTA with various forms of stress testing in adult patients presenting with suspected or confirmed stable angina.METHODS A comprehensive literature search was performed across PubMed,EMBASE,Scopus,and the Cochrane Central Register of Controlled Trials in accordance with the PRISMA guidelines.Only randomized controlled trials(RCT)published in English within the last 15 years were included.Studies involving adult patients(≥18 years)with stable angina or low-risk chest pain were selected.The intervention was CCTA,and the comparators included ECG,MPI,and stress echocardiography.Data were extracted using a standardized process,and study quality was assessed using the Cochrane Risk of Bias 2.0 tool.Due to heterogeneity in outcome measures and modalities,narrative synthesis was employed.RESULTS Five high-quality RCTs encompassing a total of 5551 patients were included.CCTA demonstrated superior diagnostic accuracy and prognostic capability across multiple studies.It was more effective in predicting major adverse cardiac events,including myocardial infarction and cardiac death,and was associated with fewer un-necessary invasive coronary angiographies and better event-free survival.Studies also reported improved revascu-larization rates in patients evaluated with CCTA,particularly within tiered diagnostic protocols.Stress testing,while useful,showed limitations in sensitivity and downstream clinical decision-making.CONCLUSION CCTA offers a diagnostically superior and clinically impactful strategy for the initial evaluation of patients with stable angina,especially those with intermediate pretest probability of CAD.Compared to conventional stress testing,it enhances risk stratification,reduces unnecessary procedures,and may improve long-term outcomes.These findings support its broader integration into diagnostic pathways for stable angina.展开更多
AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. ...AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.展开更多
AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active...AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will ...The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will occur mainly at the edges of the species ranges.We focused on the responses to climate change of the drought-resistant larch(Larix sibirica)and the moisture-sensitive Siberian pine(Pinus sibirica)along the elevation gradient in the Tannu-Ola Ridge,the southern margin where those two species coexist in Siberia by using satellite data(MODIS,Landsat,and microwave),the indexes of gross(GPP)and net(NPP)primary productivity,and tree radial growth index(GI).We found that since the warming restart in the 2000s,the area of larch-dominated forests increased by~150%while the area of pine-dominated forests decreased by~10%.The Siberian pine has retreated at low elevations(<1800 m)and increased its area at higher ones.In contrast,the area of larch stands increased in both the uphill and downhill directions.Birch(Betula spp.)also increased its area at low elevations(about+120%).Since 2001,the forested area increased by~5%.A shrubification,i.e.,an increase in the area of shrubs,was observed at high elevations.The uphill rate of timberline and shrubline migration was about 0.3 m/a.Since the 2000s,vegetation NPP has increased by 13%.A notable correlation between NPP and the GI of larch and pine was found(r=0.5-0.7).At lower elevations,NPP positively correlated with precipitation and soil moisture,while air temperature and VPD(vapor pressure deficit)increase inhibited productivity.At high elevations,the effects of these variables on productivity reversed.The continuous decline of the Siberian pine forest indicates an inevitable retreat of this species at low elevations and its replacement by larch and birch.展开更多
Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features ...Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.展开更多
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.展开更多
The issue of resistance reduction through hull ventilation is of particular interest in contemporary research.This paper presents multiphase computational fluid dynamics(CFD)simulations with 2-DOF motion of a planing ...The issue of resistance reduction through hull ventilation is of particular interest in contemporary research.This paper presents multiphase computational fluid dynamics(CFD)simulations with 2-DOF motion of a planing hull.The original hull was modified by introducing a step to allow air ventilation.Following an assessment of the hull performance,a simulation campaign in calm water was conducted to characterize the hull at various forward speeds and air insufflation rates for a defined single step geometry.Geometric analysis of the air layer thickness beneath the hull for each simulated condition was performed using a novel method for visualizing local air thickness.Additionally,two new parameters were introduced to understand the influence of spray rails on the air volume beneath the hull and to indicate the primary direction of ventilated air escape.A validation campaign and an assessment of uncertainty of the simulation has been conducted.The features offered by the CFD methodology include the evaluation of the air layer thickness as a function of hull velocity and injection flow rate and the air volume distribution beneath the hull.The air injection velocity can be adjusted across various operating conditions,thereby preventing performance or efficiency loss during navigation.Based on these findings,the study highlights the benefits of air insufflation in reducing hull resistance for high-speed planing vessels.This work lays a robust foundation for future research and new promising topics,as the exploration of air insufflation continues to be a topic of contemporary interest within naval architecture and hydrodynamics.展开更多
Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of con-sciousness(DOC) provide a model from which insights into con...Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of con-sciousness(DOC) provide a model from which insights into consciousness can be drawn. A number of recent studies highlight the difficulty in making a diagnosis in patients with DOC based only on behavioral assessments. Here we aim to provide an overview of how neuroimaging techniques can help assess patients with DOC. Such techniques are expected to facilitate a more accurate understanding of brain function in states of unconsciousness and to improve the evaluation of thepatient's cognitive abilities by providing both diagnostic and prognostic indicators.展开更多
The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen exp...The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.展开更多
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
基金supported by the Wellcome Trust(grant No.103852).
文摘The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.
文摘Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.
文摘The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.
文摘BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.
文摘Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a field and their ordered and supported effects (synergy) that must be realized for the “organized transformation” of the space and matter. Using path integrals, these transformations are decoded and their quantum principles are shown.
文摘Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography(EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.
文摘BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocardiography(ECG),myocardial per-fusion imaging(MPI),and stress echocardiography have been the first-line stra-tegies.However,coronary computed tomography angiography(CCTA),an anatomic imaging modality,is increasingly used for its ability to directly visualize coronary artery stenoses and plaque burden.Despite growing adoption,the comparative effectiveness of CCTA and stress testing in terms of diagnostic accuracy,prognostic value,and clinical outcomes in stable angina remains an area of active debate.AIM To compare the diagnostic and prognostic performance of CCTA with various forms of stress testing in adult patients presenting with suspected or confirmed stable angina.METHODS A comprehensive literature search was performed across PubMed,EMBASE,Scopus,and the Cochrane Central Register of Controlled Trials in accordance with the PRISMA guidelines.Only randomized controlled trials(RCT)published in English within the last 15 years were included.Studies involving adult patients(≥18 years)with stable angina or low-risk chest pain were selected.The intervention was CCTA,and the comparators included ECG,MPI,and stress echocardiography.Data were extracted using a standardized process,and study quality was assessed using the Cochrane Risk of Bias 2.0 tool.Due to heterogeneity in outcome measures and modalities,narrative synthesis was employed.RESULTS Five high-quality RCTs encompassing a total of 5551 patients were included.CCTA demonstrated superior diagnostic accuracy and prognostic capability across multiple studies.It was more effective in predicting major adverse cardiac events,including myocardial infarction and cardiac death,and was associated with fewer un-necessary invasive coronary angiographies and better event-free survival.Studies also reported improved revascu-larization rates in patients evaluated with CCTA,particularly within tiered diagnostic protocols.Stress testing,while useful,showed limitations in sensitivity and downstream clinical decision-making.CONCLUSION CCTA offers a diagnostically superior and clinically impactful strategy for the initial evaluation of patients with stable angina,especially those with intermediate pretest probability of CAD.Compared to conventional stress testing,it enhances risk stratification,reduces unnecessary procedures,and may improve long-term outcomes.These findings support its broader integration into diagnostic pathways for stable angina.
基金Supported by the Grants From Ligue Nationale Contre le Cancer,Comités Départementaux de la Manche,de l'Orne et du Calvados and from Université de Metz
文摘AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.
文摘AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
基金supported by the Tomsk State University Development Program(《Priority-2030》)the Basic Project of the Federal Research Center of the Scientific Center,no.FWES-2024-0023the Russian Science Foundation(project No.23-14-20015)。
文摘The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will occur mainly at the edges of the species ranges.We focused on the responses to climate change of the drought-resistant larch(Larix sibirica)and the moisture-sensitive Siberian pine(Pinus sibirica)along the elevation gradient in the Tannu-Ola Ridge,the southern margin where those two species coexist in Siberia by using satellite data(MODIS,Landsat,and microwave),the indexes of gross(GPP)and net(NPP)primary productivity,and tree radial growth index(GI).We found that since the warming restart in the 2000s,the area of larch-dominated forests increased by~150%while the area of pine-dominated forests decreased by~10%.The Siberian pine has retreated at low elevations(<1800 m)and increased its area at higher ones.In contrast,the area of larch stands increased in both the uphill and downhill directions.Birch(Betula spp.)also increased its area at low elevations(about+120%).Since 2001,the forested area increased by~5%.A shrubification,i.e.,an increase in the area of shrubs,was observed at high elevations.The uphill rate of timberline and shrubline migration was about 0.3 m/a.Since the 2000s,vegetation NPP has increased by 13%.A notable correlation between NPP and the GI of larch and pine was found(r=0.5-0.7).At lower elevations,NPP positively correlated with precipitation and soil moisture,while air temperature and VPD(vapor pressure deficit)increase inhibited productivity.At high elevations,the effects of these variables on productivity reversed.The continuous decline of the Siberian pine forest indicates an inevitable retreat of this species at low elevations and its replacement by larch and birch.
基金would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025).
文摘Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
基金supported by European Union funding(PON“Ricerca e Innovazione”2014‒2020).
文摘The issue of resistance reduction through hull ventilation is of particular interest in contemporary research.This paper presents multiphase computational fluid dynamics(CFD)simulations with 2-DOF motion of a planing hull.The original hull was modified by introducing a step to allow air ventilation.Following an assessment of the hull performance,a simulation campaign in calm water was conducted to characterize the hull at various forward speeds and air insufflation rates for a defined single step geometry.Geometric analysis of the air layer thickness beneath the hull for each simulated condition was performed using a novel method for visualizing local air thickness.Additionally,two new parameters were introduced to understand the influence of spray rails on the air volume beneath the hull and to indicate the primary direction of ventilated air escape.A validation campaign and an assessment of uncertainty of the simulation has been conducted.The features offered by the CFD methodology include the evaluation of the air layer thickness as a function of hull velocity and injection flow rate and the air volume distribution beneath the hull.The air injection velocity can be adjusted across various operating conditions,thereby preventing performance or efficiency loss during navigation.Based on these findings,the study highlights the benefits of air insufflation in reducing hull resistance for high-speed planing vessels.This work lays a robust foundation for future research and new promising topics,as the exploration of air insufflation continues to be a topic of contemporary interest within naval architecture and hydrodynamics.
基金Supported by The European Commissionthe James McDon-nell Foundation+5 种基金the European Space AgencyMind Science Foundationthe French Speaking Community Concerted Research Actionthe Belgian interuniversity attraction polethe Public Utility Foundation"Université Européenne du Travail""Fondazione Europea di Ricerca Biomedica"and the University and University Hospital of Liège
文摘Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of con-sciousness(DOC) provide a model from which insights into consciousness can be drawn. A number of recent studies highlight the difficulty in making a diagnosis in patients with DOC based only on behavioral assessments. Here we aim to provide an overview of how neuroimaging techniques can help assess patients with DOC. Such techniques are expected to facilitate a more accurate understanding of brain function in states of unconsciousness and to improve the evaluation of thepatient's cognitive abilities by providing both diagnostic and prognostic indicators.
文摘The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.
